Chronic pain impacts the lives of millions of people in significant medical and psychosocial ways. Pharmacologic treatments are steering away from chronic opioid therapy due to serious side effects, an epidemic of prescription opioid abuse, and a lack of clear long-term benefit. Therefore, nonopioid medications such as nonsteroidal antiinflammatory drugs, acetaminophen, tricyclic antidepressants, lidocaine patch, and anticonvulsants are important opioid-sparing or primary treatment options. Agents such as capsaicin, cannabis, botulinum toxin, and ketamine are less frequently prescribed adjuncts that are under active investigation to determine their roles in chronic pain therapy. Understanding the research can help the clinician determine the risks and benefits of these medications for their patients. In the future, dose and delivery optimization, combination therapy, elucidating the biology of pain, and developing novel agents will improve pharmacologic approaches to treatment.